Characterization of Porous Silicon Nanoparticles for Biomedical Applications

Porous silicon (PSi) is an intriguing material for biomedical applications because a great variation of properties can be created by adjusting fabrication parameters.Physicochemical properties, including pore size, surface area, surface chemistryand material dimensions, are dictating PSi behavior in biological environments.Degradation rate and drug loading capacity, as well as interactions with cellmembranes and blood proteins correlate with these properties. When materialdimensions are approaching the nanoscale, significant benefits, like efficient bio-distribution and permeation through biological membranes, can be achieved.Unfortunately, nanoscale objects are challenging to characterize because thephysical models that explain regularities in the nanoscale world are significantlydifferent compared with the macroscopic world. Thus, careful basic studies andlinking material properties to its performance is important when designing functional materials for biomedical applications. In this thesis, nanoparticle characterization with light scattering techniques and nanoparticle properties in biologically and pharmacologically relevant conditions are studied. During the research, we have found electrophoretic light scattering (ELS) and zeta potential to be a convenient way to characterize PSi nanoparticles’ surface chemistry and colloidal stability. Multiangle light scatterings (dynamic and static light scattering) proved to be useful phenomena when structure, agglomeration, and size of mesoporous nanoparticles needed to be revealed in their natural colloidal form. ELS studies did also show that isotonic media and peptide adsorption play a pivotal role in the stability and zeta potential of PSi nanoparticles. These results highlight the importance of medium dependent characterization of nanoparticles and show the versatility of light scattering experiments for this purpose. The role of medium in loading peptides into PSi nanoparticles has also been studied, and pH was found to have a significant effect. Despite the general assumption, the highest loading degree was achieved in pH conditions where the total charge of the peptide was close to zero. Peptide adsorption at low loading concentrations was found to be very strong, especially on hydrophobic particles, and part of the peptide payload was irreversibly adsorbed. In in vivo studies, the loading of peptides into PSi nanoparticles sustained the peptide release in subcutaneous delivery from 26 min to more than 20 hours. Intravenously administered nanoparticles did not cause notable sustained release. These results are indicating that loading conditions may affect the release of peptides from PSi nanoparticles. The possibility to tune the peptide release by altering loading conditions makes PSi nanoparticles an interesting candidate forthe sustained subcutaneous delivery of peptide drugs.Siirretty Doriast

Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

Peer reviewe

Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles’ properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles.Peer reviewe

Cooperative Heading Estimation with von Mises-Fisher Distribution and Particle Filtering

Satellite navigation has become a widely used resource in many fields. However, satellite signals are vulnerable to different interference sources, both intentional and unintentional. In safety critical situations such as rescue and tactical operations a robust alternative for Global Navigation Satellite Systems (GNSS) is needed. In this work we use magnetometers and Ultra Wideband ranging together with inertial sensors in cooperative manner for heading estimation in infrastructure independent pedestrian navigation. We utilize von Mises-Fisher distribution in order to appropriately model directions, and use a particle filter for state estimation. We demonstrate our distributed and scalable approach in two real-life tests, partially GNSS-denied outdoor navigation scenario and indoor navigation scenario. The results show that with appropriate modeling it is possible to estimate heading in a robust manner and correct for heading drift typical in footmounted pedestrian dead reckoning

Towards Baltic Sea citizenship : experiences in public involvement

The Baltic Sea is in poor shape. It is troubled by algae, increasing maritime transports, losses in biodiversity and climate change, which accelerates eutrophication. In order to change the course actions at many levels are needed. The BalticSeaNow.info project highlighted the role of individual citizens. The project aimed to arouse citizen activity and offer channels for discussion on the state and future of the Baltic Sea. The research objective was to test and develop various participation methods and ways to present research data on the Baltic Sea. This publication compiles and assess them, and provides an overview of the project on the whole

Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles

Electrostatic Interaction on Loading of Therapeutic Peptide GLP‑1 into Porous Silicon Nanoparticles

Porous silicon (PSi) nanoparticles’ tunable properties are facilitating their use at highly challenging medical tasks such as peptide delivery. Because of many different mechanisms that are affecting the interaction between the peptide and the particle, the drug incorporation into the mesoporous delivery system is not straightforward. We have studied the adsorption and loading of incretin hormone glucagon like peptide 1 (GLP-1) on PSi nanoparticles. The results show that the highest loading degree can be achieved in pH values near the isoelectric point of peptide, and the phenomenon is independent of the surface’s zeta potential. In order to study the interaction between the peptide and the nanoparticle, we studied the adsorption with lower concentrations and noticed that also non-Coulombic forces have a big role in adsorption of GLP-1. Adsorption is effective and pH-independent especially on low peptide concentrations and onto more hydrophobic nanoparticles. Reversibility of adsorption was studied as a function of buffer pH. When the loading is compared to the total mass of the formulation, the loading degree is 29%, and during desorption experiments 25% is released in 4 h and can be considered as a reversible loading degree. Thus, the peptides adsorbed first seem to create irreversibly adsorbed layer that facilitates reversible adsorption of following peptides

Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles' properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles